Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06573554
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-17
Brief Title:
Contact Cast Versus Posterior Slab as Offloading Modality for Charcot Neuroarthropathy
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Contact Cast Versus Posterior Slab as Offloading Modality for Charcot Neuroarthropathy of Foot in Diabetes OFFLOAD Study A Multicentric Non-inferiority Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Charcot neuroarthropathy CN is a condition in diabetic patients characterized by foot swelling redness and a temperature difference exceeding 2C compared to the other foot The study compares two treatments a standard knee-high non-removable total contact cast TCC and a non-removable knee-high walker Both aim to immobilize and offload the foot to promote healing The study will involve diabetic patients with specific criteria and exclude those with conditions like foot ulcers or severe kidney issues Patients will be randomly assigned to one of the two treatments and followed for up to a year The primary goal is to see how many patients achieve remission within six months with secondary goals including remission within twelve months time to remission quality of life and foot health Statistical tests will be used to analyze the data and determine the effectiveness of each treatment The study aims to improve CN treatment and provide better options for patients
Detailed Description:
Background
The etiopathogenesis of Charcot neuroarthropathy CN is intriguing since its early description in 1868 Early elucidation for the causation of CN with the neurotraumatic and neurovascular theories were accurate in their times Of late the conceptual understanding of CN has evolved after description of the role of osteoclastic resorption of foot bones by activation of receptor activator of nuclear factor kappa-B RANK The activation of RANK by RANK ligand RANKL occurs as a result of recurrent trauma to an insensate foot inciting a pro-inflammatory cascade of multiple inflammatory cytokines locally the most common being tumour necrosis factor-α TNF-α interleukin-1ß IL-1β and interleukin-6 resulting in a local cytokine storm In addition non-inflammatory factors including hyperglycemic milieu by increasing advanced glycosylation end products AGEs and autonomic neuropathy by causing a decrease in calcitonin gene-related peptide CGRP and endothelial nitric oxide synthase can upregulate the RANKL NF-кB pathway
Active CN of foot is defined clinically as a localised swelling erythema and temperature difference exceeding 2C compared to a similar site on the opposite foot The knee high non-removable total contact cast TCC is preferred as the treatment for the management of active CN
Problem Statement TCC has inherent limitations including worsening of bone mineral density BMD cast-related tissue injury shin ulcers and prolonged immobilization usually for 6 to 12 months and adversely impact the quality of life of individuals with CNO Moreover TCC is associated with sweating maceration in-TCC skin ulceration and intolerance in hot weather of tropical countries
A knee-high walker rendered non-removable is suggested as a second choice in order to immobilise and offload the foot as a conditional recommendation with low quality of evidence Presently there are no randomized controlled head-to head comparison of these non-removable knee high devices for active CNO
Hence this shall be the first study to the best of our knowledge for head-to-head comparison of two different offloading strategies for active CNO
Methods
The diagnosis of active CN shall be further corroborated by X-ray andor magnetic resonance imaging MRI 3T scanner Siemens MagnetromVerio Sanders-Frykberg classification will be used for anatomical grading and localization of the involved site of the foot A written informed consent shall be obtained from all participants
Clinical details regarding duration of symptoms inciting event diabetes duration and coexisting microvascular and macrovascular diabetic complications will be recorded Detailed neurological examination shall be performed including vibration perception threshold VPT25 mV was considered as abnormal by biothesiometer-Vibrometer-VPT1Diabetik Foot Care Madras Engineering Service India 10-g monofilament Diabetik Foot Care Madras Engineering Service India perception at 5 standardized plantar sites and ankle reflex Foot temperature shall be measured by infrared dermal thermometry FLIR Systems Inc Orlando USA with a pixel resolution of 4800 80 60 thermal sensitivity of 015C and range of detection from -20C to 250C
Blood sample for biochemistry bone turnover markers BTMs and inflammatory cytokines shall be collected after an overnight fast 8-10 hours and analysed by ECLIA
All participants will be randomised by one of the investigators at each site using computer generated randomisation blocks in 11 to either receive standardised non-walking non-removable knee high fibre-glass total contact cast group A or posterior non-removable knee high slab group B for immobilisation
All participants will be followed fortnightly and change of cast shall be performed in view of pistoning effect due to reduction of edema at each visit An average of 3 temperature recordings at the ROI of foot will be obtained after the removal of cast for 30 minutes during each follow up visit Inflammatory cytokines BTMs shall be evaluated at baseline and at clinical remission or 12 months whichever occurred earlier Clinical remission of active CN shall be defined as a temperature difference 2C between the affected foot and a similar site temperature obtained thrice on the opposite foot on two successive follow-up visits two-four weeks apart
Statistical analysis
Normality of the data for each variable shall be assessed by Kolmogorov-Smirnov test Data shall be expressed as mean SD if normally distributed and as median and inter-quartile range if skewed Student T-test shall be used to compare the means of two groups for parametric data and Mann-Whitney U test for non-parametric data Comparison of proportion of participants achieving remission shall be performed by Mc Nemar test
A Kaplan-Meier curve shall be constructed to assess the difference in remission of active CN with the interventions Cox proportion hazard model will be used to identify the association between the baseline variables and incident remission The variables are decided by their clinical relevance to active CN of foot
Sample Size 80 patients are required to be 80 sure that the upper limit of a one-sided 95 confidence interval or equivalently a 90 two-sided confidence interval will exclude a difference in favour of the TCC of more than 20
The etiopathogenesis of Charcot neuroarthropathy CN is intriguing since its early description in 1868 Early elucidation for the causation of CN with the neurotraumatic and neurovascular theories were accurate in their times Of late the conceptual understanding of CN has evolved after description of the role of osteoclastic resorption of foot bones by activation of receptor activator of nuclear factor kappa-B RANK The activation of RANK by RANK ligand RANKL occurs as a result of recurrent trauma to an insensate foot inciting a pro-inflammatory cascade of multiple inflammatory cytokines locally the most common being tumour necrosis factor-α TNF-α interleukin-1ß IL-1β and interleukin-6 resulting in a local cytokine storm In addition non-inflammatory factors including hyperglycemic milieu by increasing advanced glycosylation end products AGEs and autonomic neuropathy by causing a decrease in calcitonin gene-related peptide CGRP and endothelial nitric oxide synthase can upregulate the RANKL NF-кB pathway
Active CN of foot is defined clinically as a localised swelling erythema and temperature difference exceeding 2C compared to a similar site on the opposite foot The knee high non-removable total contact cast TCC is preferred as the treatment for the management of active CN
Problem Statement TCC has inherent limitations including worsening of bone mineral density BMD cast-related tissue injury shin ulcers and prolonged immobilization usually for 6 to 12 months and adversely impact the quality of life of individuals with CNO Moreover TCC is associated with sweating maceration in-TCC skin ulceration and intolerance in hot weather of tropical countries
A knee-high walker rendered non-removable is suggested as a second choice in order to immobilise and offload the foot as a conditional recommendation with low quality of evidence Presently there are no randomized controlled head-to head comparison of these non-removable knee high devices for active CNO
Hence this shall be the first study to the best of our knowledge for head-to-head comparison of two different offloading strategies for active CNO
Methods
The diagnosis of active CN shall be further corroborated by X-ray andor magnetic resonance imaging MRI 3T scanner Siemens MagnetromVerio Sanders-Frykberg classification will be used for anatomical grading and localization of the involved site of the foot A written informed consent shall be obtained from all participants
Clinical details regarding duration of symptoms inciting event diabetes duration and coexisting microvascular and macrovascular diabetic complications will be recorded Detailed neurological examination shall be performed including vibration perception threshold VPT25 mV was considered as abnormal by biothesiometer-Vibrometer-VPT1Diabetik Foot Care Madras Engineering Service India 10-g monofilament Diabetik Foot Care Madras Engineering Service India perception at 5 standardized plantar sites and ankle reflex Foot temperature shall be measured by infrared dermal thermometry FLIR Systems Inc Orlando USA with a pixel resolution of 4800 80 60 thermal sensitivity of 015C and range of detection from -20C to 250C
Blood sample for biochemistry bone turnover markers BTMs and inflammatory cytokines shall be collected after an overnight fast 8-10 hours and analysed by ECLIA
All participants will be randomised by one of the investigators at each site using computer generated randomisation blocks in 11 to either receive standardised non-walking non-removable knee high fibre-glass total contact cast group A or posterior non-removable knee high slab group B for immobilisation
All participants will be followed fortnightly and change of cast shall be performed in view of pistoning effect due to reduction of edema at each visit An average of 3 temperature recordings at the ROI of foot will be obtained after the removal of cast for 30 minutes during each follow up visit Inflammatory cytokines BTMs shall be evaluated at baseline and at clinical remission or 12 months whichever occurred earlier Clinical remission of active CN shall be defined as a temperature difference 2C between the affected foot and a similar site temperature obtained thrice on the opposite foot on two successive follow-up visits two-four weeks apart
Statistical analysis
Normality of the data for each variable shall be assessed by Kolmogorov-Smirnov test Data shall be expressed as mean SD if normally distributed and as median and inter-quartile range if skewed Student T-test shall be used to compare the means of two groups for parametric data and Mann-Whitney U test for non-parametric data Comparison of proportion of participants achieving remission shall be performed by Mc Nemar test
A Kaplan-Meier curve shall be constructed to assess the difference in remission of active CN with the interventions Cox proportion hazard model will be used to identify the association between the baseline variables and incident remission The variables are decided by their clinical relevance to active CN of foot
Sample Size 80 patients are required to be 80 sure that the upper limit of a one-sided 95 confidence interval or equivalently a 90 two-sided confidence interval will exclude a difference in favour of the TCC of more than 20
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None